My intent is to combine my background in microbiology and viral oncology with newer interests in cancer and herbal medicines. My objective is to initiate a productive career in research and teaching at a university or research institute that will lead to the development and clinical use of novel anticancer therapies and chemopreventive agents. The focus of this project will be mechanistic studies of herbal medicines, in particular black cohosh, on cancer in vitro and in vivo. The ideal mentor to accomplish this is Dr. I. Bernard Weinstein, who is an expert on molecular aspects of carcinogenesis and the ideal environment is Columbia University College of Physicians and Surgeons. Black cohosh, Actaea racemosa L. (= Cimicifuga racemosa), is a North American perennial in the buttercup family (Ranunculaceae) used for various women's health conditions. The overall objective of this project is to determine whether black cohosh contains components that may eventually be useful in the prevention or treatment of breast cancer. Indeed, our preliminary experiments indicate that black cohosh extracts inhibit the growth of human breast cancer cells. We will determine the pharmacokinetics of black cohosh. Partially purified extracts and specific chemicals will be examined for their effects, alone and in combination with chemotherapy agents, on the function of specific molecules that control cell growth, the cell cycle, apoptosis and the function of the ER and Her-2 receptor. Western blot analysis will be performed to examine possible effects on the expression of cyclin D1 related proteins. Luciferase reporter assays will be done to monitor effects on the transcription of NF-kB, fos, myc, jun and PPAR-g. Analytic chemical techniques will be used to identify novel compounds that might mediate these effects. To ascertain the efficacy of the compounds to treat humans, we will examine effects of an extract of black cohosh on xenografts of human breast cancer cell lines in athymic mice. This research project could identify new approaches to breast cancer prevention and therapy.